In pathophysiological terms, this disease is defined by the occurrence of recurrent seizures, each crisis being a reflection of a group of neurons’ synchronous and excessive activity. These seizures can be localised – known as focal or partial epilepsy, which represent 70% of seizures, or generalised throughout the cerebral cortex. Epilepsy can arise from any region of the cerebral cortex, as a result, there is a great variability in epileptic symptoms because they are closely related to abnormally activating neuron localisation. We therefore talk about epilepsy in the plural.
Epilepsy causes are very diverse. They can be distinguished in two major groups. On the one hand there are metabolic and structural epilepsies, also called symptomatic, induced by an injury as a result of metabolism deficits or disturbances, a tumour, an infection, central nervous system vascular disorders, or cerebral organisation abnormalities and, in particular, to cerebral cortex disorganisation.
On the other hand, we find epilepsies corresponding to brain dysfunction without structural lesion, which are often linked to genetic factors, we talk about idiopathic epilepsies. These are “genetic generalised“ epilepsies, including two sub-groups : hereditary « single gene » epilepsies, with mutation in a single major gene – which are rather rare and found in familial forms ; and common epilepsies in which several mutations in several genes in association with environment, which are involved and have a genetic predisposition of approximately 30% to 40% of epilepsies.
Epilepsy is the most common neurological disease after migraine. It has been reported to affect 0.5% to 1% of the world’s population, namely 50 million people in the world. It is estimated that about 430 000 people are affected in France, with 33 000 new cases each year. This disease affects all ages, with a higher frequency in children and elderly subjects. In 75 % of cases, the disease is established before 18. Epilepsy increases by 2 to 3 times the risk of premature death compared to the rest of the population. It can manifest as a single crisis or life-long crises. The social and familial impact of this disease is considerable.
Clinicians have many drugs at their disposal, but none is curative for now. Antiepileptic drugs aim at preventing seizures by decreasing neuronal excitability. In 30% of cases, patients do not fully or adequately respond to drug treatment. Current alternatives to these drug-resistant forms consist mainly in surgical treatment to remove the epileptogenic area, when it can be removed without major neurologic complications, or, if contraindications to the first, other surgical palliative techniques, based on cerebral or peripheral electrical stimulation. New radio surgical methods are also currently being developed.
TOPICS AND RESEARCH TEAMS
- Identify responsible genes to develop diagnostic and therapeutic tools with Eric Leguern and Stéphanie Baulac’s team.
- Understand crisis mechanisms and develop models to test new treatments with Richard Miles’ team.
- Study brain dynamics during crises, and understand their impact on cognitive processes with Stéphane Charpier’s team.
Epilepsy and cortex malformation : two mutations within the same gene
After the identification of a new gene, DEPDC5, associated with forms of focal epilepsy, Stephanie Baulac and Eric Leguern’s team has discovered that, in some cases, mutations of this gene also caused focal malformation of the cerebral cortex. This lesion could be due to a somatic mutation (neither inherited nor transmitted) of DEPDC5 that occurs in brain cells during embryonic development and adds to the mutation inherited from one’s parents. It is the first time such a mechanism is described in focal epilepsy.
Role of lipids in epileptic activity regulation
Richard Miles’ team explores sclerosis, or neuronal death, originating focal epilepsies. It is working in particular on the role of lipids, including cholesterol, in this death. In collaboration with Nathalie Cartier, Richard Miles’ team has shown that by inhibiting cholesterol release from neurons, we can increase epileptic activity and neuronal death in mice hippocampus.
Markers of an epileptic seizure ?
Epileptic seizures can happen at any time. A key question is thus the prediction and anticipation of seizures. In close interaction with clinical neurology units, Stéphane Charpier’s team has highlighted, in patients with focal epilepsy, a particular activity before the onset of seizures. Through advanced electrophysiology techniques, researchers have detected fast rhythms specific to the area triggering the seizure and recorded before the seizure occurs. These fast rhythms thus become electrophysiological markers that could, in the future, enable the development of a tool to predict epileptic seizures. This discovery is very important because it allows us to understand which mechanisms are present prior to the epileptic seizure.
Emergency treatment of seizures in patients with epilepsy
A patient in status epilepticus, an epileptic seizure which does not stop spontaneously and persisting beyond 5 minutes, should be treated as quickly as possible otherwise the brain will be damaged. In order to improve patients care, Vincent Navarro, from Stéphane Charpier’s team and several teams of the Assistance Publique have coordinated a study to test the interest of adding an immediate second antiepileptic treatment to the treatment given in emergency (benzodiazepines). This multicentric therapeutic trial has involved in France 13 pre-hospital PARAMEDIC teams and 26 hospital teams welcoming patients in status epilepticus. Vincent Navarro and his staff’s objective is to find a way to stop even more quickly epileptic patients’ seizures. This study has revealed the lack of statistically significant difference between both treatments, but it appears as a desire to improve diagnostic and therapeutic management of epileptic states, and in the perspective of strengthening specific care units, such as that of the Neuro-critical care unit at the Pitié-Salpêtrière Hospital, AP-HP.
Identify epileptic state biomarkers
Other studies are currently ongoing to identify relevant biomarkers in epileptic states, in order to identify severe neuronal damage at risk subjects. The functional consequences of the treatments used to stop epileptic states are currently being explored through a collaboration between the neurological intensive care unit, the EEG unit, and Stéphane Charpier’s team.
A smart and connected garment to diagnose seizures
It is a revolution, a smart and connected garment, Neuronaute, developed by Bioserenity, directed by Pierre Frouin, in collaboration with Michel Le Van Quyen from Stéphane Charpier’s team, opens up diagnosis possibility, remote personalised care and follow-up of patients with epilepsy. Through this technology, epilepsy follow-up would be accessible to a greater number of patients and doctors, and with lower costs. Neuronaute will be marketed in 2016.